Department of Pharmacy

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Author: search.filters.author.Mittal, AnupamaSubject: search.filters.subject.Pharmacy Department

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Now showing 1 - 4 of 4
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    Can breakthroughs in dermal and transdermal macromolecule delivery surmount existing barriers and revolutionize future therapeutics?
    (Springer, 2025-05) Mittal, Anupama; Chitkara, Deepak
    The delivery of macromolecules through dermal and transdermal routes presents both significant challenges and transformative opportunities in therapeutic applications. This review highlights the most recent advancements and innovative strategies aimed at overcoming the barriers associated with macromolecular delivery. Cutting-edge approaches such as the use of adjuvants (e.g., hyaluronic acid-based and chemical penetration enhancers), bioactive peptides with diverse functionalities, and mechanical force techniques—including iontophoresis, microneedles, and electroporation—are thoroughly explored. While various strategies have been implemented to enhance skin delivery, they often present significant challenges, particularly for macromolecules. Addressing these challenges requires integrating novel technologies and understanding the interplay between biological barriers and delivery mechanisms. Furthermore, the role of nanotechnology, through systems like nanoemulsions, polymeric nanoparticles, and transferosomes, is examined for its ability to protect macromolecules and regulate their release. Notably, this review provides unique perspectives on the interplay between these strategies and their potential to revolutionise future therapeutics. By highlighting key trends and advancements in macromolecule delivery, this review underscores the importance of innovative approaches in overcoming existing barriers and enabling efficient drug administration.
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    Simultaneous estimation of rapamycin, temozolomide and its metabolites using UPLC-ESI-MS/MS and its application to pharmacokinetics in C6-glioma bearing animals
    (Elsevier, 2025-09) Mittal, Anupama; Chitkara, Deepak
    Therapeutic drug monitoring (TDM) plays a crucial role in the optimization of drug dosage profiles and establishing an optimal balance between toxicity and its effectiveness. Developing TDM methods for simultaneous estimation of multiple molecules with diverse physiochemical properties is quite complicated and difficult to achieve. Thus, hindering the quantitative estimation for TDM and in-depth analysis from bench to clinical settings. Therefore, the current study reports a bioanalytical method for the simultaneous determination of anticancer and immunosuppressant molecules (namely rapamycin, temozolomide, and its metabolites) in a single injection using whole blood as a biological matrix.
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    cRGD-functionalized nanohybrid conjugates codelivering temozolomide and rapamycin for treating Glioblastoma multiforme: in vitro and in vivo evaluation
    (ACS, 2025-10) Mittal, Anupama; Chitkara, Deepak
    The conventional treatment of glioblastoma multiforme primarily uses Temozolomide as a chemoadjuvant alongside debulking surgery and radiotherapy; however, resistance, as well as tumor recurrence, remains a common outcome. Employing combination therapy to target multiple pathways while improving delivery with advanced systems has always been sought after. Herein, we report cRGD-functionalized hybrid polymeric nanoconjugates that could deliver Temozolomide (TMZ) and rapamycin (RAP) (cRGD-Hybrid TMZ/R NCs) as a dual payload. The cRGD-Hybrid TMZ/R NCs were thoroughly characterized, exhibiting a particle size and surface zeta potential of 141.83 nm (PDI 0.233) and −0.168 mV, respectively. The nanoconjugates carrying TMZ and RAP as dual payloads were initially screened for synergism by determining their combination index in C6 and U87MG glioma cells. Further, in vitro cell-based assays showed improved cellular uptake, cytotoxicity, and apoptotic potential of hybrid nanoconjugates. Thereafter, the cRGD-Hybrid TMZ/R NCs were evaluated in a C6-cell-induced syngeneic orthotropic glioma model in Sprague–Dawley rats, exhibiting an improved therapeutic outcome including, reduced hemispherical width (RH/LH) ratios, tumor burden, and improved survival rates compared to the free drug(s) counterpart. The histopathological evaluation indicated no major sign of toxicity in vital organs such as heart, lungs, liver, kidney, and spleen, affirming the biocompatibility of the developed cRGD-Hybrid TMZ/R nanoconjugates. In conclusion, amalgamating the cRGD cell-penetrating peptide with polymer hybrid nanoconjugates presents a better approach for delivering multiple payloads in the treatment of GBM.
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    Lipopolymeric nanoplex-mediated CRISPR/Cas9 delivery for VEGF-A knockdown in psoriatic angiogenesis
    (ACS, 2025-10) Yadav, Sushil; Mittal, Anupama; Chitkara, Deepak
    Psoriasis is a chronic, incurable inflammatory skin disease characterized by immune cell infiltration, aberrant keratinocyte differentiation, and enhanced angiogenesis. Overexpression of the vascular endothelial growth factor-A (VEGF-A) gene promotes angiogenesis and is essential for endothelial cell migration, adhesion, and proliferation. Therefore, downregulating VEGF-A represents a promising therapeutic strategy for angiogenesis-related disorders. We investigated the application of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) ribonucleoprotein complexes (sgRNA/eGFP-Cas9 RNPs) targeting VEGF-A in psoriasis. To enable efficient delivery in vitro and in vivo, we developed lipopolymeric nanoplexes (NPXs) encapsulating sgRNA/eGFP-Cas9 RNPs. These NPXs exhibited a particle size of 142.2 nm (polydispersity index: 0.144), a zeta potential of +4.27 mV, and achieved >70% transfection efficiency in HaCaT (human immortalized keratinocyte) cells. Ex vivo skin permeation studies demonstrated 66% of permeation after 24 h. The optimized NPX formulation was incorporated into a Carbopol-based gel, which displayed non-Newtonian, shear-thinning behavior with variable thixotropy and achieved 48% of skin permeation after 24 h. In vivo efficacy assessment in an imiquimod-induced psoriasis model in Swiss albino mice showed significantly improved Psoriasis Area and Severity Index (PASI) scores, reduced epidermal damage, and suppressed keratinocyte proliferation compared to naked RNPs and blank gel controls. Gene editing analysis revealed an indel frequency of 40.7% by T7 endonuclease I assay and 14% by Sanger sequencing. Enhanced cellular uptake, efficient skin permeation and retention, and improved therapeutic efficacy collectively highlight the potential of NPX-mediated CRISPR/Cas9 delivery as a noninvasive strategy for psoriasis treatment.